A comprehensive review on the effects of sex hormones on chemotherapy-induced cardiotoxicity: are they lucrative or unprofitable?

Chemotherapy is one of the routine treatment for preventing rapid growth of the tumor cells. However, chemotherapeutic agents, especially doxorubicin cause damages to the normal cells especially cardiomyocytes. Cardiotoxicity induced by chemotherapeutic drugs lead to the myocardial cell injury and finally causes left ventricular dysfunction. It seems that there were some differences in the severity of cardiovascular side effects of drugs used in the treatment of cancers. Sex hormones in male and female play crucial roles in cardiovascular development and physiological function of the heart and blood vessels. Gender differences and sex-specific hormones influence various aspects of cardiovascular health, including ventricular function, mitochondrial autophagy, and the development of abdominal aortic aneurysms. The most important gender related hormones are LH, FSH, testosterone, estrogen, progesterone, prolactin and oxytocin. They exert very important cardiovascular effects via different signaling mechanisms. Sex related hormones are also important in the cardiovascular side effects of chemotherapeutic agents, so that chronic cardiotoxicity induced by anthracyclines is more common in women. During different stages of life (before, during, and after sexual life), the levels of these hormones will be changed. This alterations can affect cardiovascular function during physiological conditions and pathological process. Because of the importance of the sex related hormones in the cardiac function, in this review we tried to comprehensively elucidate the role of these physiological hormones in cardiotoxicity induced by chemotherapeutic agents with emphasizing their signaling mechanisms.